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Obesity is a medical condition associated with a relatively high rate of morbidity, if it remains untreated.1 Weight control methods often produce short-term success, but sustained weight maintenance is difficult to attain.2,3,4 Moreover, the increasing prevalence of obesity5 requires preventive treatments of obesity. Substances that reduce energy intake without a major reduction in satiety would prove to be useful. We therefore investigated the potential of (−)-hydroxycitrate (HCA) in overweight men and women. HCA is an ingredient extracted from the rind of the fruit Garcinia cambogia, a native species from India, and is promoted as a weight loss agent. HCA is an inhibitor of ATP-citrate lyase, a cytosolic (extramitochondrial) enzyme that catalyses the cleavage of citrate to oxaloacetate and acetyl-CoA.6,7,8 Limitation of acetyl-CoA for lipid synthesis during carbohydrate feeding results in increased hepatic glycogen synthesis, which might result in reduction of energy intake.9,10 Results on the effects of HCA on appetite and body weight regulation in humans showed positive11 and negative12,13 outcomes. In this study we assessed the efficacy of HCA with respect to energy intake and satiety, hypothesizing that, when HCA is effective in reducing energy intake, satiety is sustained.

Twenty-four healthy, overweight, dietary unrestrained14,15 subjects: 12 males and 12 females (body mass index (BMI) 27.5±2.0 kg/m2; age 37±10 y) were enrolled for the trial. The Medical Ethics Committee approved of the protocol, and all subjects signed informed consent forms. During the single-blinded, randomized and placebo-controlled study, subjects consumed HCA or placebo during 2 weeks as drinks, three times per day. Before and after 2 weeks they came for 24 h energy intake, satiety and body weight assessment to the laboratory.

The drinks consisted of either 100 ml tomato juice alone or 100 ml tomato juice with HCA—500 mg SuperCitrimax/100 ml tomato juice (ie 300 mg (−)-hydroxycitrate HCA from 500 mg SuperCitrimax HCA 600 SGX dissolved). The composition of Citrimax HCA 600 SGX is 58.7% HCA, 11% calcium, 16% potassium, 1% moisture; the rest is carbohydrate and fat (EuroChem Feinchemie GmbH, München, Germany). Thus the dosage was 900 mg HCA/day. Prevention of degradation was confirmed by an efficacy study in rodents, using HCA from the same batch, showing consistent positive results twice, also 3 months after our study was finished.16 Water solubility and pH level mainly determine the bio-availability. A compound complexed with calcium and potassium is nearly 100% soluble and creates a pH level favourable for gastrointestinal absorption. Bio-availability of HCA in humans was checked by analysing the concentration of HCA in plasma.17 HCA was analysed with a concentration gradient of NaOH, starting with 0.5 mM NaOH during 2.5 min, followed by subsequent linear concentration gradients of 0.5–5 mM NaOH during 3.5 min, and 5–38.25 mM NaOH during 12 min (Dionex DX 500 chromatography system; IonPac AS 11 column 4.6×250 mm, Dionex, Sunnyvale, California, USA; flow rate 2 ml/min). Ingestion of a single dose of HCA resulted in maximal plasma HCA concentration of 1.4%,17 60–90 min after ingestion, thereafter decreasing linearly to zero over at least 3 h.17 Thus we instructed the subjects to take the drinks 1 h before lunch and dinner, and a drink 2 h after dinner, to prevent snacking in the evening.

Twenty-four-hour energy intake on the test-day after 2 weeks of treatment with HCA was significantly reduced compared to placebo, mainly due to a significant decrease in snack intake (Table 1), with a tendency to a decrease in body weight of 0.5 kg (P=0.1; Table 2). On the test-day, the appetite profile, changes in dietary restraint, taste perception, hedonics or mood did not differ with the HCA treatment compared to placebo. Reported compliance to the drinks was 90% on average, without complaints or negative effects.

Table 1: Twenty-four-hour energy intake (EI) in MJ on the test-day at the end of 2 weeks with 300 mg (−)-hydroxy-citrate/100 ml tomato juice, three times daily; or 2 weeks with placebo (100 ml tomato juice, three times daily)a

Table 2: Subject characteristics before and after 2 weeks of treatment with 300 mg (−)-hydroxycitrate/100 ml tomato juice, three times daily, or 2 weeks with placebo (100 ml tomato juice, three times daily)a

In this randomized placebo-controlled crossover design, (−)-hydroxycitrate, consumed three times daily (300 mg dissolved in tomato juice) for 2 weeks by overweight males and females, showed a significant reduction in 24 h energy intake, while satiety was sustained. The fact that the main energy intake reduction took place between meals might indicate that HCA works by increasing fat oxidation (inhibiting malonyl-CoA synthesis, thus stimulating carnitine palmitoyl transferase activity) since fat is oxidized after protein and carbohydrate, thus later during the intermeal interval.15 During this interval satiety might be sustained by increased fat oxidation and ketone body formation. We also observed a tendency toward reduction in body weight with HCA compared to placebo, but the treatment period may have been too short to result in a significant body weight loss. Our results are in line with results from a recent study by Mattes and Bormann,11 reporting a larger body weight loss in subjects using HCA for 12 weeks, compared to placebo. Reasons for the controversial results reported on HCA, may be possible degradation and bio-availability of the HCA used, which we controlled for, and timing of HCA administration according to the peak level of HCA in plasma. Also the number of obese subjects, as in the study by Heymsfield et al12 who report a negative result, may be a reason, since resistance to HCA in obese rats was shown.19

Summarizing, we showed that daily administration of a relatively low dosage of HCA (900 mg/day), during 2 weeks, reduced energy intake in overweight subjects, while satiety was sustained. HCA might not primarily be a weight loss agent, as indicated by the minor changes observed in body weight, but might be effective in preventing weight (re)gain in humans.20